Defective dystrophic thymus determines degenerative changes in skeletal muscle.
Defective dystrophic thymus determines degenerative changes in skeletal muscle.
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DOI：
10.1038/s41467-021-22305-x
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发表时间：
2021-04-08
影响因子：
16.6
通讯作者：
Torrente Y
中科院分区：
文献类型：
--
作者：
Farini A;Sitzia C;Villa C;Cassani B;Tripodi L;Legato M;Belicchi M;Bella P;Lonati C;Gatti S;Cerletti M;Torrente Y
在杜氏肌营养不良症（DMD）中，肌膜脆弱和肌纤维坏死产生吸引炎症细胞的细胞碎片。巨噬细胞和t淋巴细胞浸润肌肉，响应损伤相关的分子模式信号，TNF-α， TGF-β和白细胞介素的释放阻止骨骼肌从炎症中改善。对肌肉抗原的特异性反应和调节性T细胞（Tregs）在肌肉再生中的作用的发现扩展了这种免疫学场景。正常情况下，自身免疫是通过胸腺内的自身反应性t淋巴细胞缺失来避免的，而在外周，Tregs监测效应t细胞逃离中央调节控制。在此，我们报道了mdx小鼠胸腺结构受损，并伴有胃饥饿素表达降低、自噬功能障碍和AIRE下调。在受体裸鼠中移植营养不良的胸腺，可以确定炎症/纤维化标志物的上调，标志着代谢分解导致肌肉萎缩和力量丧失。这些结果表明，营养不良胸腺的退化通过改变中枢免疫耐受加剧了肌肉营养不良。已知免疫细胞可加重杜氏肌营养不良的炎症影响。在这里，作者描述了胸腺发育受损，并认为这种疾病模型中的胸腺退化与免疫耐受受损导致的疾病加速有关。
In Duchenne muscular dystrophy (DMD), sarcolemma fragility and myofiber necrosis produce cellular debris that attract inflammatory cells. Macrophages and T-lymphocytes infiltrate muscles in response to damage-associated molecular pattern signalling and the release of TNF-α, TGF-β and interleukins prevent skeletal muscle improvement from the inflammation. This immunological scenario was extended by the discovery of a specific response to muscle antigens and a role for regulatory T cells (Tregs) in muscle regeneration. Normally, autoimmunity is avoided by autoreactive T-lymphocyte deletion within thymus, while in the periphery Tregs monitor effector T-cells escaping from central regulatory control. Here, we report impairment of thymus architecture of mdx mice together with decreased expression of ghrelin, autophagy dysfunction and AIRE down-regulation. Transplantation of dystrophic thymus in recipient nude mice determine the up-regulation of inflammatory/fibrotic markers, marked metabolic breakdown that leads to muscle atrophy and loss of force. These results indicate that involution of dystrophic thymus exacerbates muscular dystrophy by altering central immune tolerance. Immune cells are known to aggravate the inflammatory impact of Duchene muscular dystrophy. Here, the authors describe impaired thymic development and suggest thymic involution in this model of disease is linked to disease acceleration due to impaired immunological tolerance.
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影响因子：
3.7
作者：
Einarsdottir HK;Stapleton NM;Scherjon S;Andersen JT;Rispens T;van der Schoot CE;Vidarsson G
通讯作者：
Vidarsson G
影响因子：
9
作者：
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--
影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
2.6
作者：
Eddins, Michael J.;Marblestone, Jeffrey G.;Nicholson, Benjamin
通讯作者：
Nicholson, Benjamin
影响因子：
20.3
作者：
Dixit, Vishwa D.;Yang, Hyunwon;Taub, Dennis D.
通讯作者：
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